The proposed research covers two separate, interrelated projects directed to the study of growth regulation of neoplastic colonic cells. The objectives of Project I are to study regulatory mechanisms accompanying cellular proliferation generally with emphasis on the role of enzymes of pyrimidine biosynthesis. These objectives will be pursued using primarily cultured human colonic cancer cells (HT-29) and normal human diploid cells (WI-38). Growth regulation by cyclic nucleotides and glucose will be examined for their possible relationship to pyrimidine nucleotide synthesis. Project II will focus directly on the effect of PALA (N-(phosphonacetyl)-L-aspartate), a potent and specific inhibitor of aspartate transcarbamylase, as an anti-proliferative agent of colonic cancer cells propagated in vivo (transplants) and in vitro (cell culture).